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Silica nanoparticles (SiNPs) are a new class of nanomaterials with unique properties due to their nanoscale size. Currently, SiNPs constitute a potential value in aquaculture; nonetheless, misuse induces toxicity to fisheries and ecosystems. Hence, the present prospective is a pioneer study that illustrates the acute toxicity of SiNPs to African catfish, Clarias gariepinus (B.) and the behavioral response in a renewal static system. Moreover, the influence of SiNPs on neuro-related, stress, immune-related, and oxidative stress indices was investigated. Fish groups of average body weights (73.09 ± 2.20 g) were exposed to 96-h of various concentrations of SiNPs including 0, 50, 100, 150, 200, 250, and 300 mg L⁻¹ without water exchange. The value of 96-h LC50 of SiNPs was computed using Finney's probit analysis. Here we show that the exposure of fish to SiNPs resulted in remarkable ethological alterations such as …